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Influence of Diet and Calorie Restriction on the Initiation and Promotion of Skin Carcinogenesis in the Sencar Mouse Model¹

The Eppley Institute for Research in Cancer and Allied Diseases [D. F. B., J. C. P., L. T. W., K. D., T. B.] and the Department of Biochemistry [D. F. B., J. C. P.], University of Nebraska Medical Center, Omaha, Nebraska 68198-6805

Diets were restricted to 60% of the intake of the control mice by feeding less diet (total diet restriction, TDR) or by feeding fewer calories from fat and carbohydrate (calorie restriction, CR) during the initiation or promotion phases of skin tumorigenesis in female SENCAR mice. Skin cancer was initiated by topical treatment with 10 nmol of 7,12-dimethylbenzanthracene in acetone and promoted by twice weekly treatments with 12-O-tetradecanoylphorbol-13-acetate in acetone for 20 wk. Dietary restriction preceding and during 7,12-dimethylbenzanthracene treatment did not influence skin papilloma or carcinoma yield. Papilloma incidence and the number of papillomas per effective mouse were reduced in mice restricted by both TDR and CR protocols during and following promotion with 12-O-tetradecanoylphorbol-13-acetate. Papilloma size was reduced at experimental wk 16 and 20 in both TDR and CR groups fed these diet regimens during promotion. However, by wk 28 and 32, papilloma sizes were similar in the control and TDR groups, and smaller papillomas were observed only in the CR group. The average carcinoma latency was extended by 26% in the groups restricted during promotion, and incidence was reduced in both groups. The reduction, however, was statistically significant only in the CR group. Body weight gain was reduced during the times when dietary restriction was enforced, and in a short-term study, both restricted diet treatments reduced the percentage of carcass protein.

¹ This work was supported by NIH Grants R01-CA42986 and K04-CA-01382-RCDA, American Cancer Society Grant SIG-16, and NIH Core Grant CA-36727.

² To whom requests for reprints should be addressed, at the Department of Biochemistry, University of Nebraska Medical Center, 600 S. 42^nd St., Omaha, NE 68198-6805.

Received 9/24/90. Accepted 1/23/91.

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